Serological and epidemiological investigation of Mycobacterium avium subspecies paratuberculosis in bovines in Pakistan.

Objective: To investigate the prevalence of paratuberculosis in cattle and buffaloes at twelve public dairy farms in Punjab, Pakistan. Methods: A total of 2181 more than two-year-old animals (1242 cattle and 939 buffaloes) were tested by avian tuberculin, i.e., killed purified protein derivative (PPD) of Mycobacterium avium paratuberculosis and indirect ELISA. Blood and fecal samples were collected from tuberculin positive animals. These samples were further processed by indirect ELISA. The data were analyzed using frequency analysis and logistic analysis procedures. Results: The prevalence of paratuberculosis at public dairy farms was 3.8%, as determined by tuberculin + ELISA test. It varied from 0.71-13.5% with a 100% herd prevalence. Multivariate logistic regression analysis revealed that species, milk production, total animals, total small ruminants, and total buffaloes were significantly associated with the occurrence of paratuberculosis. Odd ratio analysis revealed that with a one-kilogram increase in body weight, there will be a 0.006% increase in disease occurrence. With the increase in one animal in small ruminants and buffaloes, there will be 0.008% and 0.42% greater chances of developing paratuberculosis, respectively. Bivariate logistic regression analysis of cattle and buffaloes revealed that farm number, age, and total number of cattle were significantly associated with the occurrence of paratuberculosis. A one-month increase in lactation length increases the chance of tuberculosis by 0.004%; similarly, a one-liter increase in milk production increases the chance of disease by 10%. With each additional buffalo in the herd, there will be a 0.007% greater chance for the occurrence of paratuberculosis. Conclusion: This study concluded that tuberculin testing can be used in conjunction with ELISA to screen animals for paratuberculosis in countries with scarce resources, such as Pakistan. The efficacy of disease diagnosis can be improved by combining multiple tests.

Special function form solutions of multi-parameter generalized Mittag-Leffler kernel based bio-heat fractional order model subject to thermal memory shocks.

The primary objective of this research is to develop a mathematical model, analyze the dynamic occurrence of thermal shock and exploration of how thermal memory with moving line impact of heat transfer within biological tissues. An extended version of the Pennes equation as its foundational framework, a new fractional modelling approach called the Prabhakar fractional operator to investigate and a novel time-fractional interpretation of Fourier's law that incorporates its historical behaviour. This fractional operator has multi parameter generalized Mittag-Leffler kernel. The fractional formulation of heat flow, achieved through a generalized fractional operator with a non-singular type kernel, enables the representation of the finite propagation speed of heat waves. Furthermore, the dynamics of thermal source continually generates a linear thermal shock at predefined locations within the tissue. Introduced the appropriate set of variables to transform the governing equations into dimensionless form. Laplace transform (LT) is operated on the fractional system of equations and results are presented in series form and also expressed the solution in the form of special functions. The article derives analytical solutions for the heat transfer phenomena of both the generalized model, in the Laplace domain, and the ordinary model in the real domain, employing Laplace inverse transformation. The pertinent parameter's influence, such as α, ß, γ, a0, b0, to gain insights into the impact of the thermal memory parameter on heat transfer, is brought under consideration to reveal the interesting results with graphical representations of the findings.

Synthesis of Electrical Conductive Metal-Organic Frameworks for Electrochemical Applications.

Electrical conductivity is very important property of nanomaterials for using wide range of applications especially energy applications. Metal-organic frameworks (MOFs) are notorious for their low electrical conductivity and less considered for usage in pristine forms. However, the advantages of high surface area, porosity and confined catalytic active sites motivated researchers to improve the conductivity of MOFs. Therefore, 2D electrical conductive MOFs (ECMOF) have been widely synthesized by developing the effective synthetic strategies. In this article, we have summarized the recent trends in developing the 2D ECMOFs, following the summary of potential applications in the various fields with future perspectives.

Recent trends in wastewater treatment by using metal-organic frameworks (MOFs) and their composites: A critical view-point.

Respecting the basic need of clean and safe water on earth for every individual, it is necessary to take auspicious steps for waste-water treatment. Recently, metal-organic frameworks (MOFs) are considered as promising material because of their intrinsic features including the porosity and high surface area. Further, structural tunability of MOFs by following the principles of reticular chemistry, the MOFs can be functionalized for the high adsorption performance as well as adsorptive removal of target materials. However, there are still some major concerns associated with MOFs limiting their commercialization as promising adsorbents for waste-water treatment. The cost, toxicity and regenerability are the major issues to be addressed for MOFs to get insightful results. In this article, we have concise the current strategies to enhance the adsorption capacity of MOFs during the water-treatment for the removal of toxic dyes, pharmaceuticals, and heavy metals. Further, we have also discussed the role of metallic nodes, linkers and associated functional groups for effective removal of toxic water pollutants. In addition to conformist overview, we have critically analyzed the MOFs as adsorbents in terms of toxicity, cost and regenerability. These factors are utmost important to address before commercialization of MOFs as adsorbents for water-treatment. Finally, some future perspectives are discussed to give directions for potential research.

Unlocking the anti-diabetic potential of Gymnema sylvestre, Trigonella foenum-graecum, and their combination thereof: An in-vivo evaluation.

The current study aimed to explore the anti-diabetic effect of aqueous extracts of Gymnema sylvestre, Trigonella foenum-graecum and mixture of both the plants in alloxan-induced diabetic rabbits. A total of 30 rabbits were grouped into six equal groups as: normal control, diabetic control, diabetic treated with 300 mg/kg body weight (bw) G. sylvestre, diabetic treated with 300 mg/kg bw T. foenum-graecum, diabetic treated with 300 mg/kg bw mixture of both the plants and diabetic treated with 500 mg/kg bw metformin for 4 weeks. Diabetes was induced to all the study group animals except normal control by intravenous administration of alloxan monohydrate (80 mg/kg bw). Blood glucose was measured by glucometer and other biochemical parameters were determined through various kit methods. Serum insulin was measured through ELISA kit method. Results showed that both the plants and metformin significantly (p < .05) decreased the fasting blood glucose. Hypoglycemic activity of aqueous extract of G. sylvestre and metformin was found slightly higher than aqueous extract of T. foenum-graecum and the mixture of both the plants. However, a significant (p < .05) rise in insulin secretion was observed in studied plants extract treated rabbits. Serum urea, creatinine, and liver enzymes were found reduced significantly (p < .05) in treated rabbits whereas packed cell volume was also returned to normal in treated animals as compared to control group. The study concluded that G. sylvestre and T. foenum-graecum extracts have comparable effects with metformin in normalizing the blood glucose level and have more pronounced effect than metformin in restoring the serum biochemical parameters to normal levels. Hence, these plants may be the good alternative medicine in managing the diabetes mellitus.

Seroprevalence and haemato-biochemical effects of bovine leucosis in buffalo, Punjab, Pakistan.

Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a Deltaretrovirus belonging to the family Retroviridae. BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA) to investigate the seroprevalence of BLV through the detection of the anti-BLV gp51 antibody. A predesigned data questionnaire proforma was employed to find out the association of risk factors with disease. Overall, 18.2% of buffaloes were seropositive for BLV in the study population. The results revealed a significant association (P < 0.05) of age with BLV infection. Furthermore, milk yield and pregnancy had a significant association with the seroprevalence of BLV infection in buffalo whereas no significant association was found with sex, breeding, and health status. Biochemical and oxidative stress markers revealed a significant decrease in liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in seropositive animals as compared to healthy animals. It is concluded that BLV has a considerable prevalence in buffalo in Punjab, Pakistan and there is a dire need to investigate the disease epidemiology at both national and international levels and strategies should be developed to implement an effective control program.

Incidence of aflatoxin M1 in cows' milk in Pakistan, effects on milk quality and evaluation of therapeutic management in dairy animals.

The present study was aimed at measuring the concentration of aflatoxin M1 (AFM1) in the milk of Holstein Friesian cows, its effect on the milk quality and seasonal trends, as well as to investigate the efficacy of a commercial clay-based toxin binder. For this purpose, milk samples from dairy cows (n = 72) were collected and assayed for AFM1 before employing a clay-based toxin binder. The milk samples (n = 72) were collected from selected animals, revealing that 69.4% of the milk samples had AFM1 levels above the United States permissible limit (0.5 µg/kg). The incidence of AFM1 in milk during the winter and summer was 82.5% and 53.1%, respectively. Owing to the presence of AFM1, the level of milk fat, solids-not-fat, and protein were found to be low. Subsequently, the affected animals were divided into two groups, i.e., AFM1 positive control (n = 10) and the experimental group (n = 40). The experimental group of animals were fed the clay-based toxin binder at 25 g/animal/day. A progressive decrease of 19.8% in the AFM1 levels was observed on day 4 and on day 7 (53.6%) in the treatment group. Furthermore, the fat, solids-non-fat and protein increased significantly in the milk. In conclusion, a high level of AFM1 contamination occurs in the milk in Pakistan, affecting the quality of the milk production. Clay-based toxin binders may be used to ensure the milk quality and to protect the animal and consumer health.

Corrigendum: Sero-epidemiological study of zoonotic bacterial abortifacient agents in small ruminants.

[This corrects the article DOI: 10.3389/fvets.2023.1195274.].

Isoform switching leads to downregulation of cytokine producing genes in estrogen receptor positive breast cancer.

Objective: Estrogen receptor breast cancer (BC) is characterized by the expression of estrogen receptors. It is the most common cancer among women, with an incidence rate of 2.26 million cases worldwide. The aim of this study was to identify differentially expressed genes and isoform switching between estrogen receptor positive and triple negative BC samples. Methods: The data were collected from ArrayExpress, followed by preprocessing and subsequent mapping from HISAT2. Read quantification was performed by StringTie, and then R package ballgown was used to perform differential expression analysis. Functional enrichment analysis was conducted using Enrichr, and then immune genes were shortlisted based on the ScType marker database. Isoform switch analysis was also performed using the IsoformSwitchAnalyzeR package. Results: A total of 9,771 differentially expressed genes were identified, of which 86 were upregulated and 117 were downregulated. Six genes were identified as mainly associated with estrogen receptor positive BC, while a novel set of ten genes were found which have not previously been reported in estrogen receptor positive BC. Furthermore, alternative splicing and subsequent isoform usage in the immune system related genes were determined. Conclusion: This study identified the differential usage of isoforms in the immune system related genes in cancer cells that suggest immunosuppression due to the dysregulation of CXCR chemokine receptor binding, iron ion binding, and cytokine activity.

Detection and Phylogenetic Analysis of Extended-Spectrum ß-Lactamase (ESBL)-Genetic Determinants in Gram-Negative Fecal-Microbiota of Wild Birds and Chicken Originated at Trimmu Barrage.

Extended-spectrum ß-lactamases (ESBL) give rise to resistance against penicillin and cephalosporin antibiotics in multiple bacterial species. The present study was conducted to map genetic determinants and related attributes of ESBL-producing bacteria in three wild aquatic bird species and chickens at the "Trimmu Barrage" in district Jhang, Punjab province, Pakistan. To study the prevalence of ESBL-producing bacteria, a total of 280 representative samples were collected from wild bird species; cattle egrets (Bubulcus ibis), little egrets (Egretta garzetta) and common teals (Anas crecca) as well as from indigenous chickens (Gallus gallus domesticus) originating from a local wet market. The isolates were confirmed as ESBL producers using a double disc synergy test (DDST) and bacterial species were identified using API-20E and 20NE strips. A polymerase chain reaction (PCR) was used to detect ESBL genetic determinants and for genus identification via 16S rRNA gene amplification. A phenotypic antimicrobial susceptibility test was performed for ESBL-producing isolates against 12 clinically relevant antibiotics using the Kirby-Bauer disk diffusion susceptibility test. A phylogenetic tree was constructed for the sequence data obtained in this study and comparative sequence data obtained from GenBank. The overall prevalence of ESBL-producing bacteria was 34.64% (97/280). The highest percentage (44.28%; 31/70) of ESBL-producing bacteria was recovered from chickens (Gallus gallus domesticus), followed by little egrets (Egretta garzetta) (41.43%; 29/70), common teal (Anas crecca) (28.57%; 20/70) and cattle egrets (Bubulcus ibis) (24.28%; 17/70). Five different ESBL-producing bacteria were identified biochemically and confirmed via 16S rRNA gene sequencing, which included Escherichia coli (72; 74.23%), Enterobacter cloacae (11; 11.34%), Klebsiella pneumoniae (8; 8.25%), Salmonella enterica (4; 4.12%) and Pseudomonas aeruginosa (2; 2.06%). Based on PCR, the frequency of obtained ESBL genes in 97 isolates was blaCTX-M (51.55%), blaTEM (20.62%), blaOXA (6.18%) and blaSHV (2.06%). In addition, gene combinations blaCTX-M + blaTEM, blaTEM + blaOXA and blaCTX-M + blaSHV were also detected in 16.49%, 2.06% and 1.03% of isolates, respectively. The ESBL gene variation was significant (p = 0.02) in different bacterial species while non-significant in relation to different bird species (p = 0.85). Phylogenetic analysis of amino acid sequence data confirmed the existence of CTX-M-15 and TEM betalactamases. The average susceptibility of the antibiotics panel used was lowest for both Klebsiella pneumoniae (62.5% ± 24.42) and Salmonella enterica (62.5% ± 31.08) as compared to Enterobacter cloacae (65.90% ± 21.62), Pseudomonas aeruginosa (70.83% ± 33.42) and Escherichia coli (73.83% ± 26.19). This study provides insight into the role of aquatic wild birds as reservoirs of ESBL-producing bacteria at Trimmu Barrage, Punjab, Pakistan. Hence, active bio-surveillance and environment preservation actions are necessitated to curb antimicrobial resistance.

Molecular identification and infection pathology of Mycobacterium spp. in captive wild animals in Pakistan.

INTRODUCTION: Animal tuberculosis is an infectious, chronic, granulomatous, and debilitating disease affecting animals as well as humans. However, in recent decades, there have been many endemic geographic localities where animal tuberculosis has been identified in wildlife reservoirs, limiting the eradication program in cattle. This study aimed to identify animal tuberculosis in captive zoo animals in Pakistan. METHODOLOGY: In total, 185 morbid zoo animals were brought for postmortem examination at a veterinary postmortem facility. During the macroscopic examination, these animals were thoroughly examined for the presence of suggestive gross lesions of animal tuberculosis (granulomas/tubercles), and the pattern and distribution of these lesions in different organs. The Ziehl-Neelsen (ZN) staining was performed on smears prepared from granulomatous lesions of lung tissue followed by molecular identification of M. bovis and M. tuberculosis DNA using polymerase chain reaction (PCR). RESULTS: The postmortem examination revealed that 8.1% (15/185) of animals had gross tuberculosis lesions on the lungs and lymph nodes. The ZN staining of tissue smears showed 5.40% positivity while M. bovis and M. tuberculosis DNA was identified in 3.78 % and 1.1% of investigated animals, respectively. CONCLUSIONS: The study showed that animal tuberculosis is prevalent among wildlife in Pakistan and it may pose serious public health concerns to the people visiting these zoos and wildlife parks.

Sero-epidemiological study of zoonotic bacterial abortifacient agents in small ruminants.

Abortion is one of the leading causes of economic losses in the livestock industry worldwide. Chlamydia abortus, Coxiella burnetii, and Brucella spp. are the leading cause of late fetal loss in small ruminants. This study determined the seroprevalence of these agents in small ruminants in district Jhang. A total of 385 serum samples were taken from the sheep and goats from different flocks with a history of abortion and subjected to i-ELISA. Further, samples were analysed for liver enzymes and total serum protein using a semi-automated chemistry analyzer. The result of indirect commercial ELISA showed 13.0, 4.2 and 11.2% prevalence for Coxiella burnetii, Chlamydia abortus, and Brucella spp., respectively. Values of different serum parameters (ALT, AST, and total protein) of seropositive animals were also determined. There was a significant rise in AST and ALT values of infected animals (p ≤ 0.05). Total protein decreased for all three infections, but a significant drop was noted in Brucella positive sheep serum samples. Various risk factors were studied. Binary logistic regression proved a significant role of ticks for coxiellosis and brucellosis. Age, parity, and species did not impact the prevalence of diseases studied.

Deep learning classifiers for computer-aided diagnosis of multiple lungs disease.

BACKGROUND: Computer aided diagnosis has gained momentum in the recent past. The advances in deep learning and availability of huge volumes of data along with increased computational capabilities has reshaped the diagnosis and prognosis procedures. OBJECTIVE: These methods are proven to be relatively less expensive and safer alternatives of the otherwise traditional approaches. This study is focused on efficient diagnosis of three very common diseases: lung cancer, pneumonia and Covid-19 using X-ray images. METHODS: Three different deep learning models are designed and developed to perform 4-way classification. Inception V3, Convolutional Neural Networks (CNN) and Long Short Term Memory models (LSTM) are used as building blocks. The performance of these models is evaluated using three publicly available datasets, the first dataset contains images for Lung cancer, second contains images for Covid-19 and third dataset contains images for Pneumonia and normal subjects. Combining three datasets creates a class imbalance problem which is resolved using pre-processing and data augmentation techniques. After data augmentation 1386 subjects are randomly chosen for each class. RESULTS: It is observed that CNN when combined with LSTM (CNN-LSTM) produces significantly improved results (accuracy of 94.5 %) which is better than CNN and InceptionV3-LSTM. 3,5, and 10 fold cross validation is performed to verify all results calculated using three different classifiersConclusions:This research concludes that a single computer-aided diagnosis system can be developed for diagnosing multiple diseases.

Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line.

Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, 13CNMR, and 1HNMR,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 µg/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

Cross-Sectional Study for Detection and Risk Factor Analysis of ESBL-Producing Avian Pathogenic Escherichia coli Associated with Backyard Chickens in Pakistan.

The increasing incidence of extended-spectrum ß-lactamase (ESBL)-producing Escherichia (E.) coli in backyard chicken farming in Pakistan is of serious concern. This study aimed to assess the prevalence, antimicrobial resistance patterns and risk factors associated with ESBL avian pathogenic E. coli (APEC) isolated from backyard chickens in the Jhang district, Punjab, Pakistan. In total, 320 cloacal swabs were collected from four breeds of backyard chicken (Aseel, Golden, Misri and Necked Neck). ESBL E. coli were phenotypically identified using double disc synergy test (DDST) and corresponding genes were confirmed by multiplex polymerase chain reaction (mPCR). Out of the 320 samples, 164 (51.3%) were confirmed as E. coli, while 74 (45.1%) were characterized as ESBL E. coli. The frequency of isolation of ESBL E. coli was highest in Aseel chickens (35.1%). Of the 164 confirmed E. coli, 95.1%, 78.6%, 76.8%, 71.3%, 70.1%, 68.9%, 60.4% and 57.3% were resistant against tylosin, doxycycline, cefotaxime, enrofloxacin, colistin, trimethoprim/sulfamethoxazole, chloramphenicol and gentamicin, respectively. The ESBL gene types detected and their corresponding proportions were blaCTX-M (54.1 %, 40/74), blaTEM, (12.2%, 9/74) and co-existence (blaCTX-M and blaTEM) were shown in 33.8% (25/74). The blaCTX-M gene sequence showed homology to blaCTX-M-15 from clinical isolates. The mean multiple antibiotic resistance index (MARI) was found to be higher among ESBL E. coli (0.25) when compared to non-ESBL E. coli (0.17). Both free-range husbandry management system (p = 0.02, OR: 30.00, 95% CI = 1.47-611.79) and high antimicrobial usage in the last 6 months (p = 0.01, OR: 25.17, 95% CI = 1.81-348.71) were found significantly associated with isolation of ESBL-producing E. coli in the tested samples using binary logistic regression analysis. This study confirmed the potential of backyard chickens as a reservoir for ESBL E. coli in the Jhang district, Punjab, Pakistan.

Modular and Computational Access to Innocuous Multistep Metal-Free Synthesis of 1,3,4-Oxadiazoles as Enzyme Inhibitors.

An array of 1,3,4-oxadiazole hybrids, 7a-s, structurally intriguing cores with potential in natural product synthesis and drug discovery, have been synthesized using innovative comparable conventional and microwave-assisted protocols. The synthesis was performed by the reaction of secondary amine-based acetamides, 6a-s, as the electrophile and piperidine-based oxadiazoles as the nucleophile, 3, under the metal-free reaction conditions. High yield in minimum time with highest purity was obtained by the microwave-irradiated method instead of the conventional one. The structural elucidations were made through infrared, 1H NMR, 13C NMR, and elemental analysis studies. The whole array of synthesized compounds, 7a-s, was evaluated for their potential against α-glucosidase and butyryl cholinesterase (BChE) enzymes. Natural bond orbital and structural optimizations were made by using the B3LYP method and the basis set of 6-311++G(d,p). Frontier molecular orbitals and molecular electrostatic potential were calculated at the same level of selected compounds as potential candidates against BChE and α-glucosidase enzymes utilizing the time-dependent density functional theory. Fifteen compounds out of 19 were observed to be active against α-glucosidase enzyme in comparison with acarbose as the reference standard and 7 against the BChE enzyme compared to eserine as the reference standard. The highest potential of compound 7j against BChE is well correlated by the higher binding interaction with target protein as -10.2, calculated by docking studies. The recruited compounds against both enzymes could be the best anti-enzymatic drugs and part of drugs discovery programs after further analysis.

Correction to "Adsorption of Methyl Orange from an Aqueous Solution onto a BPPO-Based Anion Exchange Membrane".

[This corrects the article DOI: 10.1021/acsomega.2c03148.].

Recent Global Trends in Vaccinology, Advances and Challenges.

Vaccination/immunization plays a key role in maintaining the optimum health of humans and animals where the prevalence of disease is high and treatment becomes less effective [...].

Investigations of p-tolyloxy-1,3,4-oxadiazole propionamides as soybean 15-lipoxygenase inhibitors in comforting with in vitro and in silico studies.

Inflammatory disorders are the prime contributor to public health issue and the development of more effective and safer anti-inflammatory drugs in addition to other therapeutic alternatives to treat inflammatory illnesses, particularly chronic inflammatory diseases, is one of the foremost current issues. In this regard, our present work is concerned with the synthesis of a new series of N-alkyl/aralkyl/aryl derivatives (7a-o) of 5-((p-tolyloxymethyl)-4H-1,3,4-oxadiazole-2-ylthio)propionamide which was instigated by the successive conversions of p-tolyloxyacetic acid into ester, hydrazide and 5-(p-tolyloxymethyl)-4H-1,3,4-oxadiazole-2-thiol. The planned compounds (7a-o) were attained by the reaction of 5-(p-tolyloxymethyl)-4H-1,3,4-oxadiazole-2-thiol with variety of N-alkyl/aralkyl/aryl electrophiles in potassium hydroxide and were characterized by FTIR, 1H-, 13C-NMR spectroscopy, EI-MS and HR-EI-MS spectrometry and probed for their inhibiting potential against soybean 15-lipoxygenase (15-LOX) enzyme. The compounds 7a, 7n, 7 g, 7e, 7h, 7i, 7j and 7b promulgated the potent inhibiting potential with IC50 values 9.43 ± 0.45, 16.75 ± 0.49, 19.45 ± 0.37, 21.32 ± 0.46, 22.64 ± 0.56, 23.53 ± 0.62, 24.32 ± 0.45 and 29.15 ± 0.57 µM, respectively, while excellent to good inhibitory activities were shown by 7o, 7 m, 7k, 7f, 7c, 7 l and 7d with IC50 values in the range 30.29 ± 0.56 to 52.54 ± 0.64 µM. Compounds 7i-o maintained 91.12 ± 1.5 to 98.23 ± 1.2% blood mononuclear cells (MNCs) viability at 0.25 mM by MTT assay whilst compounds 7d-h observed 46.51 ± 1.3 to 57.12 ± 1.4% viability where as the most toxic compounds were 7b (12.51 ± 1.4%), 7a (28.12 ± 1.5%) and 7c (38.23 ± 1.5%) as compared with controls. Pharmacokinetic profiles predicted good oral bioavailability and drug-likeness properties of molecules as per rule of five. Molecular docking studies displayed hydrogen bonding between the compounds and the enzyme with Arg378 which was common in 7n, 7 g, 7h and baicalein. In 7a and quercetin, hydrogen bonding was established through Asn375; Tyr512 and Val589 were also involved in bonding with other analogues. RMSD (root mean square deviation) values exhibited good inhibitory profiles in the order quercetin (0.73 Å)<7 g (0.98 Å)